Electrospray ion sources have become indispensible in recent years for the chemical analysis of liquid samples by mass spectrometeric methods, owing in large part to their ability to gently create gas phase ions from sample solution species at or near atmospheric pressure. Electrospray ionization begins with the production of a fine spray of charged droplets when a liquid flows from the end of a capillary tube in the presence of a high electric field. The electric field causes charged species within the liquid to concentrate at the liquid surface at the end of the capillary, resulting in disruption of the liquid surface and the associated production of charged liquid droplets. Positive or negatively charged droplets are produced depending on the polarity of the applied electric field. Subsequent evaporation of the droplets is accompanied by the emission of gas-phase analyte ions, completing the electrospray ionization process, although the precise mechanisms involved in this last step remain unclear. Frequently, a heated gas flow is provided counter to the electrospray flow to assist the evaporation process. Some of these ions then become entrained in a small flow of ambient gas through an orifice leading into a vacuum system containing a mass spectrometer, thereby facilitating mass spectrometric analysis of the sample analyte species. Electrospray ionization sources are often coupled to mass spectrometers (ES/MS systems) as described in several U.S. Patents (for example: Fite, U.S. Pat. No. 4,209,696; Labowsky et al., U.S. Pat. No. 4,531,056; Yamashita et. al., U.S. Pat. No. 4,542,293; Henion et. al., U.S. Pat. No. 4,861,988; Smith et. al, U.S. Pat. Nos. 4,842,701 and 4,885,076; and Hail et al., U.S. Pat. No. 5,393,975), and in review articles [Fenn et. al., Science 246, 64 (1989); Fenn et. al, Mass spectrometry reviews 6, 37 (1990); Smith et. al., Analytical Chemistry 2, 882 (1990)].
The efficiency of the electrospray ionization process depends on the sample liquid flow rate, and the electrical conductivity and surface tension of the sample liquid. Typically, operation at liquid flow rates exceeding about 10-20 microliters/minute, depending on the solvent composition, leads to poor spray stability and droplets that are too large and polydisperse in size, resulting in reduced ion production efficiency Poor spray stability also results from solutions with high electrical conductivities and/or with a relatively high water content. Because electrospray ion sources are often connected to liquid chromatographs for performing LC/MS, such limitations often conflict with requirements for achieving optimum chromatography, or may even preclude the use of LC/MS for many important classes of applications. Consequently, a number of enhancements to pure electrospray have been devised in an attempt to extend the range of operating conditions that results in good ionization efficiency.
One important enhancement has been the use of a flow of gas at the end of the sample delivery tube to improve the nebulization of the emerging sample liquid. The flow of gas is often provided via the annular space between the inner liquid sample delivery tube and an outer tube coaxial with the inner tube. This approach was originally taught by Mack et al, in J. Chem Phys 52, 10 (1970), and subsequently by Henion in U.S. Pat. No 4,861,988. Essentially, with the proper relative axial positioning of the ends of the coaxial tubes, a gas flow ‘sheath’ is formed around the liquid as it emerges from the sample delivery tube, resulting in a ‘shearing’ effect that produces smaller droplets than would otherwise have been produced. By initially forming smaller droplets, a higher percent of desolvated ions results. Such configurations are referred to as pneumatic nebulization-assisted electrospray ion sources.
Optimum ionization and ion transport efficiencies generally depends on the spatial characteristics of the spray plume relative to the vacuum orifice, which, in turn, depends on operational parameters such as the sample liquid and nebulizing gas flow rates and the physicochemical characteristics of the sample liquid. Hence, an ability to properly locate the ends of the sample delivery and nebulizing gas tubes relative to the vacuum orifice is important. The terminal portions of the coaxial tubes are typically housed within a mechanical support structure, commonly referred to as the electrospray ‘probe’, which protrudes into the enclosed housing of the electrospray ion source. Such probes are often provided with linear and rotational positioning mechanisms to re-optimize the position of the spray plume as the spatial distribution of the plume changes from one analysis to another. Provisions are also often provided for adjusting the relative axial positions of the ends of the sample liquid delivery tube and the coaxial nebulizing gas tube, which may optimize differently depending on the liquid sample characteristics and operating parameters.
While such mechanical adjustments have proven essential for source optimization, nevertheless, the process of achieving maximum performance via such adjustments has frequently been found to be quite tedious. Furthermore, once an optimum configuration is achieved for a particular analysis, it is generally not guaranteed that optimum performance will be reproducible with the same configuration for the same analysis at a later time, especially subsequent to any changes to the source configuration in the interim. One reason for such difficulties lies in the relatively poor control that exists in current electrospray probes over the concentricity between the coaxial sample delivery and nebulizing gas tubes. Typically, the sizes of such tubes are relatively small, being typically on the order of fractions of a millimeter, and the annular gap between the outer diameter of the inner sample delivery tube and the inner diameter of the outer nebulizing gas tube is typically even smaller, often on the order of only tens of micrometers. Hence, maintaining accurate concentricities between these two coaxial tubes has been challenging.
Perhaps even more difficult is maintaining the concentricity constant as the relative axial positions of the ends of the tubes is adjusted. Currently, this adjustment in present sources is generally accompanied by a rotation of the inner sample delivery tube about the axis of the nebulizing gas tube. Hence, any eccentricity between the axes of the sample delivery and nebulizing gas tubes rotates as the relative axial positions of the ends of the tubes is adjusted. The effect of any such eccentricity is to cause the flow of nebulizing gas to be cylindrically assymetric with respect to the axis of the liquid sample emerging from the sample delivery tube. Hence, enhancement of the sample nebulization by the nebulizing gas will be different on different sides of the spray plume, and, perhaps worse, this asymmetry in the spray nebulization rotates about the plume as the relative axial positions of the tube ends is adjusted. The net result is that optimization of the electrospray ion source configuration and operating parameters has been tedious and often ineffective, and has led to poor reproducibility and often poor stability during operation. Accordingly, there is a need for a pneumatical nebulization-assisted electrospray probe with improved ease of use, stability, and reproducibility.
Further, the nature of the materials from which the inner sample delivery tube and the outer nebulizing gas tube are fabricated often influences the quality and stability of the resulting electrospray due to chemical, electrochemical and/or electrostatic interactions with the sample, and/or compatibility with upstream chromatic separation schemes. Hence, different materials have been used, both electrically conductive as well as dielectric, depending on the types of applications and instrument configuration employed. Generally, if different materials are required, an entirely different probe would be necessary, because the design of prior art probes has not provided the capability of easy and rapid exchange of individual parts. Therefore, there has been a need to eliminate the unnecessary expense of utilizing different probes depending on the application.